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作者

Sun Z. Zhong X.-L. Zong Y. Wu Z.-C. Zhang Q. Yu J.-T. Tan L.

作者单位

Department of Geratology, Qingdao Municipal Hospital, Taishan Medical University, China Department of Neurology, Qingdao Central Hospital, China Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China

刊名

CNS and Neurological Disorders - Drug Targets

年份

2015

卷号

Vol.14 No.3

页码

378-385

ISSN

1871-5273

关键词

Adenosine Agonist Amygdala-kindled Blood-brain barrier Epilepsy Phenytoin

摘要

Drug resistance in epilepsy is considered as a complicated and multifactorial problem. Poor penetration of antiepileptic drugs across blood-brain barrier into the brain, which results in insufficient level of the drugs at the targeted brain region, has been discussed as one mechanism contributing to pharmacoresistance of epilepsies. Therefore, modulating permeability of BBB is the effective treatment strategy since it facilitates the entry of AEDs into the central nervous system . Recently, si...更多

Drug resistance in epilepsy is considered as a complicated and multifactorial problem. Poor penetration of antiepileptic drugs across blood-brain barrier into the brain, which results in insufficient level of the drugs at the targeted brain region, has been discussed as one mechanism contributing to pharmacoresistance of epilepsies. Therefore, modulating permeability of BBB is the effective treatment strategy since it facilitates the entry of AEDs into the central nervous system . Recently, signaling through receptors for the adenosine has been identified as a potent modulator of BBB permeability. This paper aimed to investigate the effects of auxiliary application of adenosine receptor agonist on amygdala-kindled seizures in adult male Wistar rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, rats were randomly divided into three groups: control, phenytoin, and phenytoin + 5'-N-ethylcarboxamidoadenosine groups. NECA was applied to the PHT+NECA group after the administration of PHT . Intravenous infusion of NECA resulted in a significant increase in brain PHT levels as compared with the PHT treatment alone. On the other hand, the auxiliary application of NECA dramatically decreased the frequency of generalized seizures and seizure stage, shortened duration of afterdischarge and generalized seizures, as well as the elevated the afterdischarge threshold and generalized seizures threshold. Our study demonstrated that auxiliary application of AR agonist enhanced brain antiepileptic drug levels and strengthened the anticonvulsant properties of PHT against amygdala kindled seizures.收起

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